Pathways synthesis from cysteine

Taurine is a dietary essential in the cat, which is an obligate carnivore with a limited capacity for taurine synthesis from cysteine. On a taurine-free diet, neither supplementary methionine nor cysteine will maintain normal plasma concentrations of taurine, because cats have an alternative pathway of cysteine metabolism reaction with mevalonic acid to yield felinine (3-hydroxy-1,1-dimethylpropyl-cysteine), which is excreted in the urine. The activity of cysteine sulfinic acid decarboxylase in cat liver is very low. 

The third reason for favoring a non-radical pathway is based on studies of a mutant version of the CFeSP. This mutant was generated by changing a cysteine residue to an alanine, which converts the 4Fe-4S cluster of the CFeSP into a 3Fe-4S cluster (14). This mutation causes the redox potential of the 3Fe-4S cluster to increase by about 500 mV. The mutant is incapable of coupling the reduction of the cobalt center to the oxidation of CO by CODH. Correspondingly, it is unable to participate in acetate synthesis from CH3-H4 folate, CO, and CoA unless chemical reductants are present. If mechanism 3 (discussed earlier) is correct, then the methyl transfer from the methylated corrinoid protein to CODH should be crippled. However, this reaction occurred at equal rates with the wild-type protein and the CFeSP variant. We feel that this result rules out the possibility of a radical methyl transfer mechanics and offers strong support for mechanism 1. 

Plants and bacteria produce the reduced sulfur required for the synthesis of cysteine (and methionine, described later) from environmental sulfates the pathway is shown on the right side of Figure 22-13. Sulfate is activated in two steps to produce 3-phosphoadeno-sine 5 -phosphosulfate (PAPS), which undergoes an eight-electron reduction to sulfide. The sulfide is then used in formation of cysteine from serine in a two-step pathway. Mammals synthesize cysteine from two amino acids methionine furnishes the sulfur atom and serine furnishes the carbon skeleton. Methionine is first converted to 5-adenosylmethionine (see Fig. 18-18), which can lose its methyl group to any of a number of acceptors to form A-adenosylhomocysteine (adoHcy). This demethylated product is hydrolyzed to free homocys-... 

The thiazole ring is assembled on the 5-carbon backbone of 1-deoxyxylulose 5-phosphate, which is also an intermediate in the alternative biosynthetic pathway for terpenes (Fig. 22-2) and in synthesis of vitamin B6 (Fig. 25-21). In E. coli the sulfur atom of the thiazole comes from cysteine and the nitrogen from tyrosine.374 The same is true for chloroplasts,375 whereas in yeast glycine appears to donate the nitrogen.372 The thiamin biosynthetic operon of E. coli contains six genes,372a 376 one of which (ThiS) encodes a protein that serves as a sulfur carrier from cysteine into the thiazole.374 The C-terminal glycine is converted into a thiocarboxylate ... 

Figure 14.7. Pathways for the synthesis of taurine from cysteine. Cysteine sulfinate decarboxylase, EC 4.1.1.29 cysteic acid decarboxylase, EC 4.1.1.29 (glutamate decarboxylase, EC 4.1.1.15) cysteine oxidase, EC 1.13.11.20 cysteamine oxygenase, EC 1.13.11.19 and hypotaurine oxidase, EC 1.8.1.3. Relative molecular masses (Mr) cysteine, 121.2 cysteamine, 77.2 cysteine sulfinic acid, 153.2 cysteic acid, 169.2 hypotaurine, 109.1 and taurine, 125.1.

Serine, glycine, and cysteine are dispensable (or nonessential) amino acids because they can be biosynthesized from precursors that are readily available in the body Serine can be made from or converted back to glucose, and also is used in the synthesis of cysteine. The pathways for these conversions are detailed in Chapter 8. 

Fig. 3. Synthesis of taurine from cysteine. The major pathway for the formation of taurine is via hypotaurine.

S ATP + 4-methyl-5-(2-hydroxyethyl)thiazole <1, 2> (<1> enzyme involved in biosynthesis of thiamine [1] <1> the bifunctioinal enzyme hydroxyethylthiazole kinase/thiamine-phosphate pyrophosphorylase catalyzes two sequential steps in the synthesis of thiamin monophosphate from hydroxyethylthiazole [2] <2> the enzyme is a salvage enzyme in the thiamin biosynthetic pathway and enables the cell to use recycled 4-methyl-5-j8-hydroxyethylthiazole as an alternative to its synthesis from 1-deoxy-o-xylulose-5-phosphate, cysteine, and tyrosine [3]) (Reversibility <1, 2> [1,2,3]) [1,2, 3]... 

These results are consistent with the hypothesis that the sulfur atom of DCS is derived from cysteine and carbon atoms 1 and 2 are derived from serine. Biosynthesis of DCS would then follow the well known [8]serine palmityol CoA pathway with introduction of the sulfur atom into sphingosine or ceramide by a cystathionine-type reaction with cysteine followed by oxidation of the SH group to a sulfonic acid group The role of cysteic acid is not clear, since it cannot participate in a cystathionine-type reaction, but it may be a more effective donor of sulfur than sulfate for synthesis of cysteine from serine. 

Fig. 5. Regulation of the enzymes of methionine biosynthesis and related pathways. Enzymes catalyzing the synthesis of methionine and 5 -adenosylmethionine (SAM) from cysteine are (1) cystathionine y-synthase, (2) j9-cystathionase, (3) methionine synthase, and (4) SAM synthetase. Enzymes associated with the synthesis and metabolism of phospbohomoserine which are relevant to the regulation of methionine synthesis are (5) aspartate kinase, (6) homoserine kinase, and (7)...

Figure 8.3 A summary of pathways involved in the synthesis of non-essential amino acids. Glutamate is produced from ammonia and oxoglutarate. Glutamate is the source of nitrogen for synthesis of most of the amino acids. Cysteine and tyrosine are different because they require the essential amino acids (methionine and phenylyalanine) for their synthesis. These two amino acids are, therefore, conditionally essential, i.e. when there is not sufficient methionine or phenylyalanine for their synthesis, they are essential (Details are in Appendix 8.2).

Cysteine is formed in plants and in bacteria from sulfide and serine after the latter has been acetylated by transfer of an acetyl group from acetyl-CoA (Fig. 24-25, step f). This standard PLP-dependent (3 replacement (Chapter 14) is catalyzed by cysteine synthase (O-acetylserine sulfhydrase).446 447 A similar enzyme is used by some cells to introduce sulfide ion directly into homocysteine, via either O-succinyl homoserine or O-acetyl homoserine (Fig. 24-13). In E. coli cysteine can be converted to methionine, as outlined in Eq. lb-22 and as indicated on the right side of Fig. 24-13 by the green arrows. In animals the converse process, the conversion of methionine to cysteine (gray arrows in Fig. 24-13, also Fig. 24-16), is important. Animals are unable to incorporate sulfide directly into cysteine, and this amino acid must be either provided in the diet or formed from dietary methionine. The latter process is limited, and cysteine is an essential dietary constituent for infants. The formation of cysteine from methionine occurs via the same transsulfuration pathway as in methionine synthesis in autotrophic organisms. However, the latter use cystathionine y-synthase and P-lyase while cysteine synthesis in animals uses cystathionine P-synthase and y-lyase. 

Figure 25-6 Postulated pathways for synthesis of the black pigment melanin and pigments (phaeomelanins) of reddish hair and feathers. Dopachrome reacts in two ways, with and without decarboxylation. The pathway without decarboxylation is indicated by green arrows. To the extent that this pathway is followed the green carboxylate groups will remain in the polymer. The black eumelanin is formed by reactions at the left and center while the reddish phaeomelanin is derived from polymers with cysteine incorporated by reactions at the right.

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